The disorders that are called glaucoma cause a progressive loss of retinal ganglion cells (RGC) and their axons, which initially leads to loss of peripheral vision, and ultimately leads to complete blindness. It is estimated that glaucoma will affect about 80 million people worldwide in year 2020. Worldwide, glaucoma is the second-leading cause of blindness after cataracts, and it is the leading cause of blindness among African Americans. Glaucoma has a significantly higher prevalence in people of more than 60 years of age than in younger people.
Glaucoma disorders can be divided into two categories: “open-angle glaucoma” and “closed-angle glaucoma”. Open-angle glaucoma is painless and develops slowly over time and has no symptoms until the disease has progressed significantly. Closed-angle glaucoma causes sudden pain, redness, nausea and vomiting with the intraocular pressure suddenly increasing, causing a medical emergency. Closed-angle glaucoma accounts for less than 10 percent of glaucoma cases in the United States and as many as half of all glaucoma cases in some Asian countries. The Merck Manual, 18th Edition, 2006, pages 903-910, describes different types glaucoma and the signs and symptoms of glaucoma.
The underlying cause of glaucoma is unknown. However, the single major risk factor, and the major focus of treatment, is elevated intraocular pressure (IOP). Intraocular pressure, also called ocular pressure, is a function of two factors: the production of the aqueous humor from the ciliary processes of the eye and the drainage of the same fluid out of the eye through the trabecular meshwork. The diagnosis of glaucoma includes measurements of intraocular pressure (tonometry), anterior chamber angle examination (gonioscopy), and examination of the optic nerve for visible damage. Elevated IOP is believed to lead to damage of the optic nerve and is therefore considered to be a causative factor for the development of glaucoma.
IOP is often increased because the drainage of the fluid in the eye through the trabecular mesh is impaired. Preservative compounds, and particularly benzalkonium chloride (BAK) that are presently used in ocular formulations have been shown to damage the trabecular mesh at concentration that are 100 times lower than the concentrations presently used in dropper-bottles by glaucoma patients. Thus, for diseases related to increased IOP such as glaucoma, it is critical to develop preservative-free therapeutic formulations.
What is needed are compositions and methods for reducing elevated intraocular pressure, with and without concomitant glaucoma, in therapeutically effective formulations that are free from preservatives.